. Author manuscript; available in PMC: 2022 May 13.

Published in final edited form as: Nat Rev Gastroenterol Hepatol. 2020 Dec 17;18(4):252–268. doi: 10.1038/s41575-020-00386-1

Table 4 |.

Challenges in producing iPSC-derived cells for HBL-MPS

iPSC-derived cells	Status	Importance
Hepatocyte-like cells	Maturation protocols are needed to produce the full hepatic metabolic profile	Necessary to mimic all aspects of human liver disease and function; immature iPSC-derived hepatocytes typically have less metabolic capacity and consume only 25% of the oxygen⁸⁹
Cholangiocyte-like cells	Cholangiocytes that closely resemble the in vivo transcriptional and functional features have been generated but require further testing and validation^223,224	Enables various applications, such as developmental studies, disease modelling, therapeutic target validation and drug screening
LSEC-like cells	No protocols have yet been reported for the generation of LSECs	LSECs have unique properties that affect endocytosis, permeability, vascular tone, portal pressure, regeneration and inflammation^225–227
VECs	VECs have been generated and shown to have basic functionality but need further testing in MPS²²⁸	Involved in immune, haematological and transport processes
Hepatic stellate-like cells	A robust protocol has been generated^100,218 but cells need further testing in MPS	Stellate cells play a key role in the initiation, progression and regression of liver fibrosis^146,229
Macrophage-like (Kupffer) cells	Human iPSC-derived macrophages perform immunological functions with similar transcriptome profiles as primary cells²¹⁷	Scavenger and phagocytic functions to remove protein complexes, small particles, senescent cells and debris^143,230
Adaptive immune cells	Several reports of iPSC-derived antigen-specific cytotoxic T lymphocytes and NK cells with high proliferative capacity and expression of central memory T cell markers²³¹ but with immature phenotype	Adaptive immune response to mimic inflammatory response, adoptive immunotherapy, etc.

HBL-MPS, human biomimetic liver microphysiology system; iPSC, inducible pluripotent stem cell; LSEC, liver sinusoidal endothelial cell; NK, natural killer; VEC, vascular endothelial cell.